The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies.
The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies.
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DOI：
10.1158/1055-9965.epi-15-0247
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Thibodeau SN
中科院分区：
文献类型：
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作者：
Beebe-Dimmer JL;Hathcock M;Yee C;Okoth LA;Ewing CM;Isaacs WB;Cooney KA;Thibodeau SN
HOXB 13基因中一种罕见的非保守取代（G84 E）已被证明与前列腺癌的风险相关。对来自马约诊所生物库（MCB）中男性患者的DNA样本进行基因分型，以确定G84 E突变的频率及其与各种癌症的相关性。使用定制的TaqMan（Applied Biosystems）G84 E（rs 138213197）测定法对受试者进行基因分型。除了捐献血液标本外，所有MCB参与者还完成了基线问卷调查，以收集有关病史和癌症家族史的信息。9,012名男性患者中有49名为G84 E携带者（0.5%）。31%（n= 2，595）的参与者被诊断患有癌症，包括51.1%的G84 E携带者，而非携带者仅为30.6%（p=0.004）。与未患癌症的男性相比，G84 E在患有前列腺癌的男性中最常见（p<0.0001）。然而，该突变在膀胱癌（p=0.06）和白血病（p=0.01）男性中也更常见。G84 E携带者与非携带者相比更可能有一级前列腺癌阳性家族史（36.2% v. 16.0%，p=0.0003）。我们的研究证实了HOXB 13 G84 E变异与前列腺癌之间的关联，并提示G84 E与白血病之间存在新的关联，并提示与膀胱癌之间存在关联。未来的研究有必要确认这些关联，以提高我们对生殖系HOXB 13突变在人类癌症中作用的理解。HOXB 13与前列腺、白血病和膀胱的相关性表明该基因在肿瘤发生中具有重要作用。
A rare non-conservative substitution (G84E) in the HOXB13 gene has been shown to be associated with risk of prostate cancer. DNA samples from male patients included in the Mayo Clinic Biobank (MCB) were genotyped to determine the frequency of the G84E mutation and its association with various cancers. Subjects were genotyped using a custom TaqMan (Applied Biosystems) assay for G84E (rs138213197). In addition to donating a blood specimen, all MCB participants completed a baseline questionnaire to collect information on medical history and family history of cancer. Forty-nine of 9,012 male patients were carriers of G84E (0.5%). Thirty-one percent (n=2,595) of participants had been diagnosed with cancer, including 51.1% of G84E carriers compared to just 30.6% of non-carriers (p=0.004). G84E was most frequently observed among men with prostate cancer compared to men without cancer (p<0.0001). However, the mutation was also more commonly observed in men with bladder cancer (p=0.06) and leukemia (p=0.01). G84E carriers were more likely to have a positive family history of prostate cancer in a first degree relative compared to non-carriers (36.2% v. 16.0%, p=0.0003). Our study confirms the association between the HOXB13 G84E variant and prostate cancer and suggests a novel association between G84E and leukemia and a suggestive association with bladder cancer. Future investigation is warranted to confirm these associations in order to improve our understanding of the role of germline HOXB13 mutations in human cancer. The associations between HOXB13 and prostate, leukemia and bladder suggest that this gene is important in carcinogenesis.